The A. fumigatus genome contains 2 caspase genes, but their function is completely unknown. Since caspase-induced cell death in higher eukaryotes is a stress response that removes damaged cells for the benefit of the individual as a whole, our lab hypothesizes that caspases contribute to filamentous growth by allowing the organism to sacrifice nutrient-deprived or damaged hyphae for the benefit of the invasive growth of the colony periphery. In this project, the activity of two A. fumigatus caspases, CasA and CasB, will be measured in response to stress conditions, and their contribution to mycelial growth will be determined. The role of caspase activity to fungal growth in the host will be determined by testing mutants deleted for casA and casB for alterations in virulence, fungal burden or dissemination in a mouse infection model. The regulation of fungal caspase activity will be determined, focusing on levels of control that are well established for mammalian caspases, including caspase processing, intracellular localization and alternative splicing. [unreadable] [unreadable]